The present invention relates generally to the field of implantable medical devices, and more particularly pertains to sensors that may be implanted into a body to elicit at least one of a mechanical, chemical or electrical response to an in vivo physiological condition or state with the body. The present invention provides a vacuum deposited film which may be either a monolithic monolayer of material or a multilayered film having at least portions of the film capable of sensing at least one of changes in temperature, pressure, or the presence or absence of chemical or biochemical species in the body by mechanical, electrical, chemical, electrochemical or electromechanical means.
Specifically, the present invention relates to the manufacture and use of implantable sensors to monitor physical, chemical or electrical parameters of a fluid flow through a body passageway. For example, the sensors of the present invention may be employed to provide volumetric measurements, flow rate measurements, pressure measurements, electrical measurements, biochemical measurements, temperature, measurements, or measure the degree and type of deposits within the lumen of an endoluminal implant, such as a stent or other type of endoluminal conduit. The present invention also provides a means to modulate mechanical and/or physical properties of the endoluminal implant in response to the sensed or monitored parameter. For example, where the monitored blood flow volume through an endoluminal device is determined to be below physiological norms and/or the blood pressure is determined to be above physiological norms, the stent may be actuated to increase its diameter, such as by superelastic properties of the stent materials.
Post-implantation evaluation of the patency of an endoluminal device presently requires clinical examination by angiography or ultrasound. The results of these tests provide a qualitative evaluation of device patency. It is, therefore, desirable to provide a means for quantitatively measuring the post-implantation patency of an endoluminal device on either a periodic or continuous basis. Quantitative in vivo measurements of volumetric flow rate, flow velocity, biochemical constitution, fluid pressure or similar physical or biochemical property of the body fluid through an endoluminal device would provide more accurate diagnostic information to the medical practitioner.
As used herein, the term “endoluminal device” is intended to include stents, grafts and stent-grafts which are implanted within an anatomical passageway or are implanted with a body to create a non-anatomical passageway between anatomically separated regions within the body. Endoluminal devices in accordance with the present invention may include endovascular devices, prostatic devices, urethral devices, cervical devices, esophageal devices, intestinal devices, biliary devices, intra-cardiac devices, valves, hepatic devices, renal devices or devices with similar application within the body.
The term “sensor,” as used in this application, is intended to include, without limitation, biosensors, chemical sensors, electrical sensors and mechanical sensors. While the term “biosensor” has been used to variously describe a number of different devices which are used to monitor living systems or incorporating biological elements, the International Union for Pure and Applied Chemistry (IUPAC) has recommended that the term “biosensor” be used to describe “a device that uses specific biochemical reactions mediated by isolated enzymes, immunosystems, tissues, organelles or whole cells to detect chemical compounds usually by electrical, thermal or optical signals” 1992, 64, 148 IUPAC Compendium of Chemical Terminology 2nd Edition (1997). The term “chemical sensor” is defined by the IUPAC as a device that transforms chemical information, ranging from concentration of a specific sample component to total composition analysis, into an analytically useful signal. Conventional biosensors are a type of chemical sensor that consists of three basic elements: a receptor (biocomponent), transducer (physical component) and a separator (membrane or coating of some type). The receptor of a chemical sensor usually consists of a doped metal oxide or organic polymer capable of specifically interacting with the analyte or interacting to a greater or lesser extent when compared to other receptors. In the case of a biosensor the receptor or biocomponent converts the biochemical process or binding event into a measurable component. Biocomponents include biological species such as: enzymes, antigens, antibodies, receptors, tissues, whole cells, cell organelles, bacteria and nucleic acids. The transducer or physical component converts the component into a measurable signal, usually an electrical or optical signal. Physical components include: electrochemical devices, optical devices, acoustical devices, and calorimetric devices as examples. The interface or membrane separates the transducer from the chemical or biocomponent and links this component with the transducer. They are in intimate contact. The interface separator usually screens out unwanted materials, prevents fouling and protects the transducer. Types of interfaces include: polymer membranes, electropolymerized coatings and self-assembling monomers.
Sensors should have high selectivity and sensitivity, have rapid recovery times with no hysteresis, long lifetimes if not single use, low drift, automated calibration, self-diagnostic, low cost, no reagent additions required and no sample preparation. It is obvious that presently available chemical sensors and biosensors do not meet these criteria (World Biosensor Market, Frost and Sullivan, Report 5326-32, 1997). National Institute of Standards and Technology, Nano-and MEMS Technologies for Chemical Biosensors (A231 Administration Building, Gaithersburg, Md. 20899) found at www.atp.nist.gov/atp/focus/98wp-nan.htm.
In the clinical diagnostic market, various sensor designs are known including electrochemical sensors (potentiometric ISEs; amperometric; conductometric; miniaturized ISEs; field effect transistors; interdigitated transistors); optical sensors using fiber-optic or surface plasmon resonance technologies; acoustic sensors such as piezo-crystal and surface acoustic wave sensors; and thermal sensors which employ thermistors. Thus, it is known to employ microfabrication techniques to make clinical sensors. Currently, the most commercially successful microfabricated sensor in the clinical diagnostic market is the MEDISENSE glucose meter that uses an electrochemical transduction of an enzymatic reaction. However, the need for in vivo sensing systems is well recognized. Work on in vivo sensing systems for both glucose and lactate has confirmed the effectiveness of phospholipid copolymers in improving hemocompatibility. Fisher, U., et al. Biosen. Bioelectron., 10, xxiii (1995).
By their nature, implantable sensors must have some mechanism for communicating sensed information from the sensor to a reader, which may be human or machine, outside the body. Since it is impractical to implant a physical connection between the sensor and the external reader, alternative means for generating a readable signal external the body must be provided. Suitable means for generating a readable signal external the body include, without limitation, radiographically visible signals, magnetic flux signals, chemical signals, chemifluorescent signals, and/or electrical signals.
The pathogenesis of arteriosclerosis has not been positively identified. A number of risk factors, such as high cholesterol, hypertension, and diabetes are known to serve to turn on inflammatory mechanisms at the arterial wall and recruit white cells into the arterial wall to ultimately cause the formation and breakdown of plaque, which, in turn, lead to clinical events. The process starts out with oxidation-sensitive nuclear regulatory mechanisms. Free radicals control the genes that cause the synthesis of proteins that are expressed in the endothelial cells and serve to attract white cells into the arterial wall.
Endothelialization of an implanted medical device has been the subject of considerable scientific study and literature. It is know known that various growth factors and cytokines are responsible for activating smooth muscle cell receptors and initiating smooth muscle cell proliferation. Endothelial cell growth factors such as fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) have been identified as significant for endothelial cell growth in vitro. While VEGF is specific for endothelial cells, FGFs also stimulate smooth muscle cell growth. Bauthers, C., Growth Factors as a Potential New Treatment for Ischemic Heart Disease, Clin. Cardiol. 20:11-52-11-57 (1997).
It has been recognized that there is a need for an in vivo sensor capable of sensing binding of endothelial cells or arterioschlerotic plaque, and providing an ex vivo detectable signal, without requiring external or internal power sources.